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J Heart Lung Transplant. 2012 Aug;31(8):865-73. doi: 10.1016/j.healun.2012.04.008. Epub 2012 May 30.

Type I immune response cytokine-chemokine cascade is associated with pulmonary arterial hypertension.

Author information

1
Division of Pulmonary, Critical-Care, Allergy & Immunology; David Geffen School of Medicine, Ronald Reagan-University of California Los Angeles Medical Center, CA 90095, USA. dross@mednet.ucla.edu

Abstract

BACKGROUND:

Perivascular infiltrating mononuclear cells have been described in the vasculopathy found in multiple types of pulmonary arterial hypertension (PAH). We determined the expression of a specific type 1 immune response cytokine-chemokine cascade-interleukin (IL)-18 → (monokine induced by γ-interferon [MIG]/chemokine [C-X-C motif] ligand [CXCL] 9, interferon γ-induced protein [IP]-10/CXCL10 and interferon-inducible T-cell α chemoattractant [ITAC]/CXCL11)-in plasma samples from individuals with World Health Organization (WHO) Group 1 PAH.

METHODS:

We analyzed cytokine and chemokine protein levels in plasma from 43 individuals with WHO Group 1 PAH by enzyme-linked immunosorbent assay compared with 35 healthy individuals. Immunohistochemical studies on tissue specimens from WHO Group 1 PAH patients were performed for cytokines and chemokines and their respective receptors.

RESULTS:

Plasma IL-18 levels from WHO Group 1 PAH patients were significantly increased compared with healthy controls. Downstream chemokine CXCL10, but not CXCL9 or CXCL11, was markedly elevated compared with controls. Cellular sources of IL-18 were medial but not intimal smooth muscle cells. IL-18Rα was expressed from medial smooth muscle cells, endothelial cells, and mononuclear cells. CXCL10 and its main receptor, CXCR3, were expressed from infiltrating vascular wall mononuclear cells.

CONCLUSIONS:

These data suggest that augmented expression of IL-18 and CXCL10 may perpetuate an inflammatory milieu that eventually contributes to the vascular obstruction characteristic of PAH.

PMID:
22658713
DOI:
10.1016/j.healun.2012.04.008
[Indexed for MEDLINE]
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